The mucosa of the female reproductive tract (FRT) is the front-line of defense against sexually transmitted infections (STIs) for women. The risk of STIs is increased in the presence of inflammation and dependent on numerous mucosal environmental factors. These latter include the mucosal immune components and the vaginal microbiota, which interact to modulate inflammation. It is known that the menstrual cycle significantly modifies the FRT mucosa, but its impact on immune & inflammatory markers and the vaginal microbiota has received little attention.

To shed light on this aspect of women's health, researchers from IDMIT's Immunity and Transmission Laboratory (CEA-Jacob) published an article in Frontiers in Immunology describing how inflammation and the composition of the vaginal microbiota evolve across the menstrual cycle. They performed their study in a non-human primate model, specifically cynomolgus macaques. Indeed, female non-human primates and humans have similar reproductive systems and menstrual cycles, making the former pertinent models for the study of STI infection, diseases course and prophylaxis in the latter.

The longitudinal study covered three menstrual cycles, over which the research team observed cytokine profiles and characterized the various populations of neutrophils. Cytokines are soluble proteins produced during inflammation. They alert neutrophils, a first-responder of the immune system. Those neutrophils activate, migrate toward the site of inflammation and interact with other immune cells. The team's results showed that FRT cytokine concentrations do vary over the menstrual cycle, with a production peak during menstruation. The IDMIT study was the first to characterize the different cervicovaginal neutrophil populations and follow their course over the menstrual cycle. That effort demonstrated in increase in a particular neutrophil subpopulation during menstruation. The researchers also observed changes in the vaginal microbiome's bacterial composition over the menstrual cycle.

This work demonstrates the significant impact menstruation has on the local FRT environment, with increases in cytokine production, changes to the microbiota and the recruitment of mature/activated neutrophils. Its results underline the need to consider the menstrual cycle in future studies focused on female animal and/or human reproductive tract mucosae, and particularly on STI susceptibility and in the setting of vaccinal or therapeutic research. Thereto, the IDMIT team is now turning its attention to studying the impact of vaginal microbiota modifications on inflammation and susceptibility to infection by Chlamydia trachomatis, a very frequent STI in young women. Another project is looking at the influence of vaginal Chlamydia infection on local inflammation and HIV-1/AIDS coinfection.

Collectively, these studies may enable novel strategies targeting inflammation or immune cells with the ultimate goal of developing preventative therapies against STIs.